Fatty Acid Metabolism Suberate

Ibipinabant (IBI), a potent cannabinoid-1 receptor (CB1R) antagonist, previously in development for the treatment of obesity, causes skeletal and cardiac myopathy in beagle dogs. This toxicity was characterized by increases in muscle-derived enzyme activity in serum and microscopic striated muscle degeneration and accumulation of lipid droplets in myofibers. Additional changes in serum chemistry included decreases in glucose and increases in non-esterified fatty acids and cholesterol, and metabolic acidosis, consistent with disturbances in lipid and carbohydrate metabolism...

L-bifunctional enzyme (Ehhadh) is part of the classical peroxisomal fatty acid β-oxidation pathway. This pathway is highly inducible via peroxisome proliferator-activated receptor α (PPARα) activation. However, no specific substrates or functions for Ehhadh are known, and Ehhadh knockout (KO) mice display no appreciable changes in lipid metabolism. To investigate Ehhadh functions, we used a bioinformatics approach and found that Ehhadh expression covaries with genes involved in the tricarboxylic acid cycle and in mitochondrial and peroxisomal fatty acid oxidation...

The purpose of the current study was to assess the effects of long-term exposure to low levels of DDVP on the biochemical parameters and metabolic profiles of rats. Three different doses (2.4, 7.2, and 21.6 mg/kg body weight/day) of DDVP were administered to rats through their drinking water over 24 weeks. Significant changes in blood cholinesterase, creatinine, urea nitrogen, aspartate aminotransferase, alanine aminotransferase, and albumin concentrations were observed in the middle and high dose groups. Changes in the concentration of some urine metabolites were detected via ultra performance liquid chromatography-mass spectrometry (UPLC-MS)...

Suberin, a cell specific, wall-associated biopolymer, is formed during normal plant growth and development as well as in response to stress conditions such as wounding. It is characterized by the deposition of both a poly(phenolic) domain (SPPD) in the cell wall and a poly(aliphatic) domain (SPAD) thought to be deposited between the cell wall and plasma membrane. Although the monomeric components that comprise the SPPD and SPAD are well known, the biosynthesis and deposition of suberin is poorly understood...

Soybean (Glycine max L. Merr.) is a versatile and important agronomic crop grown worldwide. Each year millions of dollars of potential yield revenues are lost due to a root rot disease caused by the oomycete Phytophthora sojae (Kaufmann & Gerdemann). Since the root is the primary site of infection by this organism, we undertook an examination of the physicochemical barriers in soybean root, namely, the suberized walls of the epidermis and endodermis, to establish whether or not preformed suberin (i.e. naturally present in noninfected plants) could have a role in partial resistance to P...

We reported a male infant with multiple acyl CoA dehydrogenase deficiency, probably due to electron transfer flavoprotein dehydrogenase deficiency. He was noted to have severe muscle weakness, a high serum creatine kinase (CK) level up to 6920 IU/L, lipid storage myopathy and fatty liver at 6 months of age. A GC/MS analysis of urinary organic acids showed excess excretion of dicarboxylic acids, including glutaric, 2-hydroxyglutaric, adipic, suberic, sebacic, malonic, ethylmalonic and methylsuccinic acids. On a urinary acylglycine analysis, hexanoylglycine and suberylglycine were increased, but not isovalerylglycine, in amount...

PURPOSE: Women appear to be more vulnerable to developing alcoholic liver disease than men. In rats, we previously found that the response of certain pathways of fatty acid metabolism to alcohol feeding was less efficient in females than in males, resulting in striking accumulation of fatty acids in the liver of the female rats. We sought to determine whether similar differences occurred in humans. PATIENTS AND METHODS: Urinary excretion of medium chain (C6-C10) dicarboxylic acids (final products of fatty acid omega-oxidation) was determined in 40 recently drinking alcoholic subjects (24 men and 16 women) and 21 nonalcoholic subjects (12 men and nine women)...

A 12 week old female Labrador retriever dog with signs of progressive diffuse degeneration of the brain and spinal cord was found to have methylmalonic and malonic aciduria. Over a 5 month period, the dog developed neurologic signs compatible with disease of the central nervous system with predominant diffuse cerebral and right lateralizing brainstem deficits. Gross pathological examination of the brain showed that the lateral, third, and fourth ventricles of the brain were markedly enlarged and associated with white and grey matter atrophy...

Long-chain acyl-CoA dehydrogenase (LCAD) deficiency is an autosomal recessive disorder of fatty acid metabolism characterized by hypoglycemia, muscle weakness and hepato- and cardiomegaly to varying extents. Analysis of organic acids in urine usually reveals dicarboxylic aciduria with elevated levels of adipic, suberic and sebacic acids as well as longer chain dicarboxylic acids. Correct diagnosis of suspected patients requires measurement of LCAD in tissue or preferably, white blood cells and/or cultured skin fibroblasts...

Administration of decanoic acid to rats resulted not only in elevated urinary excretions of the C10-dicarboxylic acid (sebacic acid), but also in highly elevated excretions of the beta-oxidation products C8- and C6-dicarboxylic acids (suberic and adipic acids). Activation of the lipid metabolism by starvation, fat-feeding and experimental diabetes increased the excretions of adipic acid and decreased the excretions of sebacic acid, i.e. the rate of oxidation of fatty acids was correlated to the adipic : sebacic acid ratio in urine...

The abnormal metabolites-adipic, suberic, and sebacic acids-were detected in large amounts in the urine of a boy during a Reye's syndrome-like crisis. Substantial amounts of 5-OH-caproic acid, caproylglycine, glutaric acid, and 3-OH-butyric acid and moderately elevated amounts of ethylmalonic acid, methylsuccinic acid, 3-OH-isovaleric acid, and isovalerylglycine were also found. These metabolites were consistently present in urine samples collected in the boy's habitual condition after the attack. 1-[14C]-Palmitic acid was oxidized at a normal rate, whereas U-[14C]-Palmitic acid was oxidized at a reduced rate in cultured skin fibroblasts from the patient, thus indicating a defect at the level of medium- and/or short-chain fatty acid oxidation...

By means of gas chromatographic methods substantial amounts of the C6-C10-dicarboxylic acids, i.e. adipic, suberic and sebacic acids, have been found in the urine from children with unexplained attacks of lethargy and hypotonia, presumably related to episodes of fever and/or insufficient food intake. The course have once been fatal and is often characterized by severe hypoglycemia without ketonuria. Systematic gas chromatographic/mass spectrometric determinations of selected organic acid metabolites in the urine, together with enzymatic measurements in fibroblasts and clinical data from 4 patients of this category, have shown that the biochemical basis of this syndrome can be inborn errors of the beta-oxidation of fatty acids, localized to the medium-chain acyl-CoA dehydrogenation system...

Two boys, who are not related, with hypoglycemia and C6-C10-dicarboxylic aciduria were investigated. Besides substantial amounts of adipic, suberic and sebacic acids, the urinary metabolic profile of organic acids contained 5-OH-caproic acid and caproylglycine. During acute attacks the concentrations of adipic, suberic and sebacic acids were 300--530, 160--200 and 35--200 micrograms/mg creatinine, respectively, and the excretions of 5-OH-caproic acid and caproylglycine were 75--330 and 41--260 micrograms/mg creatinine, respectively...

A 7-year-old boy developed a severe unilateral grand mal seizure at the age of 5 years (phenobarbitone therapy); 1.5 years later valproate (2-propylpentanoic acid, VPA) was added to the therapy. After a seizure-free period of 3 months the patient died from hepatic failure resembling Reye syndrome. Several plasma and urine samples from the final stage before and during peritoneal dialysis were analyzed by GC/MS. The predominant feature was the abnormally increased formation of both 3 mono- and 4 double unsaturated metabolites of VPA amounting in plasma to 58%-71% of the sum of VPA plus all analyzed metabolites (controls maximal 15%) and in urine to 34%-61% (controls maximal 10%)...

Urine from 12 patients with Reye syndrome was examined by gas-liquid chromatography for identification of organic acids. Large amounts of lactic acid, dicarboxylic acids (adipic, suberic, and sebacic), and 3-OH butyric acid were noted. The mean (+/- SD) total dicarboxylic acid concentration was 0.98 +/- 0.24 mg/mg creatinine, compared with 0.006 +/- 0.010 mg/mg creatinine in controls, n = 140; the mean in patients with Reye syndrome was higher (1.40 +/- 0.26 mg/mg creatinine, n = 8) when the samples were obtained prior to initiation of therapy, but declined rapidly after administration of hypertonic glucose, exchange transfusion, and osmotic diuretics...

Most of the patients with carnitine-palmitoyl-transferase deficiency (CPT) show reduced levels of blood ketone bodies in the postabsorptive state. In the present study, we have evaluated ketone body and glucose kinetics in patients with CPT deficiency. Intermediate metabolites of carbohydrate and lipid metabolism have also been studied. Ketone body (KB) turnover was measured by means of sequential intravenous bolus injections of 3-14C acetoacetate and 3-14C D(-) 3-hydroxybutyrate in four patients with liver, platelet, and muscle deficiency of CPT system and in eight normal overnight fasting subjects...

Dicarboxylic aciduria caused by enhanced or inhibited fatty acid metabolism is usually described as increased urinary excretion of saturated medium-chain dicarboxylic acids, such as adipic, suberic, and sebacic acids. Besides these saturated acids, increased excretion of unsaturated dicarboxylic acids is also observed. However, the structural identities of these unsaturated dicarboxylic acids are largely unknown. Using synthetic authentic samples, dual capillary column gas-liquid chromatography, and capillary column gas-liquid chromatography-mass spectrometry, we have identified these acids as trans-2-hexenedioic, trans-3-hexenedioic, cis-3-octenedioic, cis-4-octenedioic, and trans-3-octenedioic acids...

In recent years, the metabolism of triglycerides has attracted much attention. Oxidation of fatty acids is an essential energy supply, especially when glucose supply is limited. In the present study, the effect of a 3-day high medium-chain triglyceride (MCT; 51% of calories), low carbohydrate intake on plasma glucose and amino acid, and urinary organic acid levels, including dicarboxylic and tricarboxylic acid cycle intermediates, was determined in eight normal adult volunteer subjects. Urine was collected at baseline and at 48 to 72 hours for amino acid and organic acid levels, and plasma collected at 0 and 72 hours for glucose and amino acid concentration...

Previously, we [Jin, S.-J., & Tserng, K.-Y. (1989) J. Lipid Res. 30, 1611-1619] reported the structures of urinary octenedioic acids occurring in patients with dicarboxylic aciduria. We proposed that these unsaturated octenedioic acids were derived from the oxidation of oleic and linoleic acids. By comparison with synthetic decenedioic acids, we have further identified the higher homologues of unsaturated dicarboxylic acids in urine as cis-5-decenedioic (c5DC10), cis-4-decenedioic (c4DC10), cis-3-decenedioic (cDC10), trans-4-decenedioic, trans-3-decenedioic, cis-5-dodecenedioic (c5DC12), cis-3-dodecenedioic (c3DC12), and trans-3-dodecenedioic acids...

Riboflavin-deficient rats are used to study the metabolism of deuterium-labeled nonanoic acids under conditions mimicking the human disorder of multiple acyl-CoA dehydrogenase deficiency in which large amounts of ethyl-malonic, glutaric, adipic, suberic, 4-octenedioic, sebacic and 4-decenedioic acids are excreted. Both control and deficient rats convert the nonanoic acids to labeled azelaic and pimelic acids. The labeling pattern in pimelic acid is consistent with the omega-oxidation of nonanoic acids to azelaic acid followed by beta-oxidation to pimelic acid...